Ceftolozane antibiotic compositions
This disclosure provides pharmaceutical compositions comprising ceftolozane, pharmaceutical compositions comprising ceftolozane and tazobactam, methods of preparing those compositions, and related methods and uses of these compositions.
1. A solid pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium, said composition comprising less than 0.15% of a compound of formula (III)
relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored for 1 month at a temperature of 25° C. and at a relative humidity of 60%, wherein the ceftolozane sulfate and tazobactam sodium provide ceftolozane active and tazobactam active in a ratio of 2:1 by weight.
2. The composition of claim 1 , which contains less than 0.1% of the compound of formula (III) relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored for 1 month at a temperature of 25° C. and at a relative humidity of 60%.
3. The composition of claim 1 , which contains less than 0.03% of the compound of formula (III) relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm when stored for 1 month at a temperature of 25° C. and at a relative humidity of 60%.
4. The composition of claim 1 , wherein the amount of ceftolozane active is 1,000 mg and the amount of tazobactam active is 500 mg.
5. The composition of claim 1 , wherein the amount of ceftolozane active is 2,000 mg and the amount of tazobactam active is 1,000 mg.
6. The pharmaceutical composition of claim 1 , comprising 1,147 mg ceftolozane sulfate and 537 mg tazobactam sodium.
7. The composition of claim 1 , which is provided in a unit dosage form.
8. An injectable composition comprising the pharmaceutical composition of claim 1 dissolved in a pharmaceutically acceptable vehicle.
9. A pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium, said composition comprising less than 0.15% of the compound of formula (III)
relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, and less than 1.5% of a compound of formula (IV)
relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored for 3 months at a temperature of 25° C. and at a relative humidity of 60%, wherein the ceftolozane sulfate and tazobactam sodium provide ceftolozane active and tazobactam active in a ratio of 2:1 by weight.
10. The composition of claim 9 , which contains less than 0.05% of the compound of formula (III) relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored for 3 months at a temperature of 25° C. and at a relative humidity of 60%.
11. An injectable composition comprising the pharmaceutical composition of claim 9 dissolved in a pharmaceutically acceptable vehicle.
12. A pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium, said composition comprising less than 0.15% relative to ceftolozane sulfate of the compound having a mass spectra depicted in FIG. 14 , as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored for 1 month at a temperature of 25° C. and at a relative humidity of 60%, wherein the ceftolozane sulfate and tazobactam sodium provide ceftolozane active and tazobactam active in a ratio of 2:1 by weight.
13. The composition of claim 12 , which contains less than 0.1% relative to ceftolozane sulfate of the compound with the mass spectra depicted in FIG. 14 , as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored for 1 month at a temperature of 25° C. and at a relative humidity of 60%.
14. The composition of claim 12 , which contains less than 0.03% relative to ceftolozane sulfate of the compound with the mass spectra depicted in FIG. 14 , as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored for 1 month at a temperature of 25° C. and at a relative humidity of 60%.
15. The composition of claim 12 , wherein the amount of ceftolozane active is 1,000 mg and the amount of tazobactam active is 500 mg.
16. The composition of claim 12 , wherein the amount of ceftolozane active is 2,000 mg and the amount of tazobactam active is 1,000 mg.
17. The pharmaceutical composition of claim 12 , comprising 1,147 mg ceftolozane sulfate and 537 mg tazobactam sodium.
18. An injectable composition comprising the pharmaceutical composition of claim 12 dissolved in a pharmaceutically acceptable vehicle.
19. A pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium, said composition comprising less than 0.15% relative to ceftolozane sulfate of a compound having a mass spectra depicted in FIG. 14 , as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, and less than 1.5% of a compound of formula (IV):
relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored for 3 months at a temperature of 25° C. and at a relative humidity of 60%, wherein the ceftolozane sulfate and tazobactam sodium provide ceftolozane active and tazobactam active in a ratio of 2:1 by weight.
20. An injectable composition comprising the pharmaceutical composition claim 19 dissolved in a pharmaceutically acceptable vehicle.